The purpose of this project is to develop new experimental models for an approach to the immunotherapy of cancer which appear to hold considerable promise, but which have not yet been applied to the clinic: the possibilities of adoptive immunotherapy with lymphoid cells sensitized to neoplastic cells in vitro (effector cells) and expanded to large quantities with TCGR, in combination with other therapeutic regimens. We will focus largely on the therapeutic efficacy of effector cells generated and propagated in vitro. The tumors employed will include non-immunogenic radiation or radiation leukemia virus (RadLV)-induced thyumomas and low immunogenic, spontaneous lung and mammary carcinomas. Sensitization of lymhoid cells from normal or tumor-bearing hosts will be carried out in macro "one-way" mixed lymphocyte-tumor cell cultures (MLTC) Lymphoblasts will be isolated from the sensitized lymphoid cell preparations and expanded 1000 - 100,000,000 fold with semi-purified T-cell growth factor (TCGF), over a period of 2-8 weeks. The cultured cytotoxic lymphocytes, and cloned lines derived from them, will be administered to mice with advanced disseminated neoplastic disease in conjunction with various therapeutic regimens, including surgical excision, chemotherapy, radiotherapy, and bone-marrow transplantation of syngeneic or allogeneic cells. Once adequate experimenal information hasaccrued, our efforts will turn to studies of how to utilize this method for treating cancer patients.